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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Alkylation of a hydrophilic photosensitizer enhances the contact-dependent photo-induced oxidation of phospholipid membranes

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Vignoni, Alejandro [1] ; Layana, Carla [2] ; Junqueira, Helena C. [3] ; Thomas, Andres H. [4] ; Itri, Rosangela [5] ; Baptista, Mauricio S. [3] ; Vignoni, Mariana [4]
Total Authors: 7
[1] Univ Politecn Valencia, IU Automat & Informat Ind Ai2, Synthet Biol & Biosyst Control Lab, Cami Vera S-N, Valencia 46022 - Spain
[2] Univ Nacl La Plata, Fac Cs Exactas, Ctr Reg Estudios Genom, Blvd 120 Nr 1459, RA-1900 La Plata - Argentina
[3] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo - Brazil
[4] Univ Nacl La Plata, CCT La Plata CONICET, Dep Quim, Inst Invest Fisicoquim Teor & Aplicadas, RA-1900 La Plata - Argentina
[5] Univ Sao Paulo, Inst Fis, Dept Fis Aplicada, BR-05508090 Sao Paulo - Brazil
Total Affiliations: 5
Document type: Journal article
Source: DYES AND PIGMENTS; v. 187, MAR 2021.
Web of Science Citations: 0

Lipophilic photosensitizers able to photo-induce lipid oxidation in biomembranes are, in general, much more efficient than hydrophilic ones; acting through the formation of singlet oxygen (O-1(2)), which oxidizes the fatty acid double bonds (type II mechanism). Here we investigate the binding and photosensitizing properties of 4-(decyloxy)pteridin-2-amine (O-decyl-Ptr) using unilamellar vesicles of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), a phospholipid with monounsaturated fatty acids. By means of molecular dynamic (MD) simulations, we showed that O-decyl-Ptr binds to the membrane in a localization that favors the direct reaction of the triplet excited state of O-decyl-Ptr with DOPC double bonds. As a consequence, although O-1(2) is formed, O-decyl-Ptr acts mainly as a contact-dependent photosensitizer, meaning through radical formation (type I mechanism). Mass spectrometry analysis of vesicles irradiated in the presence of O-decyl-Ptr, demonstrated the generation of alcohols (LOH), ketones (LO) and hydroperoxides (LOOH). In agreement with the mechanistic hypothesis proposed, LOH and LO (type I photooxidation products) are formed faster than LOOH (type II photooxidation product). Interestingly, no short-chain oxidized products were detected. Accordingly, membrane fluctuations and formation of filaments and buds are observed during in-situ photo-activation of O-decyl-Ptr in giant unilamellar vesicles due to changes in membrane spontaneous curvature. Finally, we evaluated the effect of the photochemical processes studied at a cellular level and demonstrated in experiments of viability of mammalian cells that O-decyl-Ptr has important photodynamic properties. Similar experiments performed using the hydrophilic photosenstizer pterin (Ptr) show that alkylation leads to a striking increase in the efficiency of photosensitized lipid oxidation. (AU)

FAPESP's process: 19/12957-4 - Membrane photodamage by new lipophilic lumazine derivatives
Grantee:Rosangela Itri
Support type: Research Grants - Visiting Researcher Grant - International
FAPESP's process: 16/04296-0 - Photosensitization and photodamage of cells and biomimetic models by pterin derivatives
Grantee:Mauricio da Silva Baptista
Support type: Research Grants - Visiting Researcher Grant - International
FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 12/50680-5 - Photosensitization in life sciences
Grantee:Mauricio da Silva Baptista
Support type: Research Projects - Thematic Grants